In order to carry out the aims of the NIDA PSOCenter, we are requesting a 5-year competing renewal with support for the 5 current Cores (Administrative, Animal, Biochemical Pharmacology, Cell and Immunology, Integrative Pharmacology, and Molecular Biology) and the addition of a new Core, the Analytical Core. The Center has enhanced productivity, synergy, and interdisciplinary research, and enabled recruitment of new faculty into the field of drugs of abuse. Major integrative themes include 1) Study of drugs of abuse and their endogenous ligands, particularly opioids and cannabinoids, in regulation of pain, body temperature, and the immune system;research addresses and compares basic mechanisms responsible for changes in these systems produced by both acute and chronic administration, and 2) Drug interactions-as individuals rarely abuse a single drug, it is important to determine whether interactions occur among abused drugs such as opioids, cocaine, and marijuana, and to assess if the types of interactions are similar in the different systems. Experimental results are built on evolving theories of drug interactions. The scope of the ongoing projects in the Center marries in vivo and in vitro approaches that examine effects of drugs at the cellular, biochemical, molecular and whole-organism levels. Integration of information ranging from measurements of behavior to gene activation has stimulated collaborations leading to novel hypotheses and results. The Cores of the P30 Center have fostered multidisciplinary interactions resulting in a true intellectual integration leading to hypothesis building and implementation of lines of experimentation never previously conceived. While the focus of the NIDA P30 Center is basic research, clinical faculty have become interested in the potential for translational research in the area of drug abuse. Temple University has made major commitments that will sustain growth in the area of drug abuse research in the future. The Cores are providing the technical expertise to facilitate this transition in a cost-efficient way. The P30 Center is the glue that holds together and attracts others to our group of outstanding scientists. Work fostered by the Center has given us national visibility in the areas of drug interactions and neuroimmunopharmacology.